Chromosome 1 alterations most frequently resulting in the duplication of the long arm material tend to occur at a late stage in tumor development and appear to be associated with the progression of all forms of cancer. Human papillomavirus (HPV) immortalized cell lines derived from human foreskin keratinocyte or exocervical cells exhibit non-random structural alterations of chromosome 1. This study demonstrates that chromosome 1 rearrangements are also early alterations associated with cell immortality or transition to the malignant phenotype in cervical neoplasia. Fluorescence in situ hybridization (FISH) allows mapping of single-copy genes and direct visualization of integrated or episomal viral DNA. With this method, cellular sequences flanking an HPV-16 integration site from a cervical carcinoma were localized at 14q32.3 near the loci of akt-1 and elk-2 proto-oncogenes. The human herpesvirus-6 (HHV-6) genome was detected by FISH in cervical carcinoma C4-1 cells infected with HHV-6 as multiple randomly distributed hybridization signals representing episomal sites associated with the chromosomes. This first localization of HHV-6 sequences on human chromosomes shows that the state of the viral genome can be determined at single-cell level. Rat mdr1b gene was localized by FISH on chromosome 4q12. This localization at a single chromosome band will permit the identification of synteny groups on rat, mouse and human genome. Other newly isolated genes, the human type 1 (acidic) keratin gene and the gene for the human transcriptional repressor GCF were mapped on chromosomes 17p12, 17q11.2-12 and 2q12, respectively. Other human type 1 keratin gene clusters are at the same sites on chromosome 17. In addition, several genes implicated in carcinogenesis such as p53 gene and two members of the erb gene family are located in the same region of the short and long arm of chromosome 17. GCF gene location at 2q12 is close to the band affected in the 2;8 variant translocation in Burkitt's lymphoma and in anomalies observed in lymphoblastic leukemias.
